Kivonat:
Aβ25-35, the fibril-forming, biologically active toxic fragment of the full-length amyloid β-peptide also forms fibrils on mica by an epitaxial assembly mechanism. Here we investigated,
by using atomic force microscopy, nanomechanical manipulation and FTIR spectroscopy, whether the epitaxially-grown fibrils display structural and mechanical features similar to the
ones evolving under equilibrium conditions in bulk solution. Unlike epitaxially-grown fibrils, solution-grown fibrils displayed a heterogeneous morphology and an apparently helical
structure. While fibril assembly in solution occurred on a time scale of hours, on mica surface fibrils appeared within a few minutes. Both types of fibrils showed a similar plateau-like
nanomechanical response characterized by the appearance of force staircases. The IR spectra of both fibril types contained an intense peak between 1620 and 1640 cm-1 indicating that β-
sheets dominate their structure. A shift in the amide I band towards greater wavenumbers in epitaxially assembled fibrils suggests that their structure is less compact than that of solution grown fibrils. Thus, equilibrium conditions are required for a full structural compaction.
Epitaxial Aβ25-35 fibril assembly, while significantly accelerated, may trap the fibrils in less compact configurations. Considering that under in vivo conditions the assembly of amyloid fibrils is influenced by the presence of extracellular matrix components, the ultimate fibril
structure is likely to be influenced by the features of underlying matrix elements.
